Process for the preparation of cis-(1r,2s)-methyl dihydrojasmonate by asymmetric catalytic hydrogenation

Abstract

The application belongs to the technical field of organic synthesis, and specifically discloses a method for preparing cis(1R, 2S)-methyl dihydrojasmonate through asymmetric catalytic hydrogenation, and specifically comprises the following steps: taking 3-oxo-2-pentyl-1-cyclopentene-1-methyl acetate as raw material, under the action of an asymmetric catalytic hydrogenation catalyst, a chiral ligand and an additive, in a solvent, in a hydrogen atmosphere with a certain pressure, selectively performing asymmetric catalytic hydrogenation reaction on a carbon-carbon double bond to generate cis(1R, 2S)-methyl dihydrojasmonate, and obtaining a finished product after rectification of a crude product. The reaction condition is mild, the synthesis process route is simple, a high proportion of cis(1R, 2S)-methyl dihydrojasmonate is obtained after rectification after the reaction is completed, the product has high selectivity, and there are few by-products.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology and relates to the synthesis of methyl cis(1R,2S)-dihydrojasmonic acid, a fragrance compound, specifically one such compound. Background Technology

[0002] Methyl dihydrojasmonate (MDJ) is a colorless or pale yellow transparent liquid belonging to the jasmone family. It possesses a fresh and elegant jasmine fragrance with a pleasant and soft lemon-like fruity aroma. Its long-lasting scent makes it a highly sought-after and important synthetic fragrance compound favored by perfumers. It is widely used in high-end perfumes, cosmetics, food flavorings, and daily detergent fragrances, and its usage and volume are continuously increasing. Methyl dihydrojasmonate was first marketed by Firmenich in Switzerland under the trade name "Hedione." Europe is the largest market for methyl dihydrojasmonate, currently growing at a rate of 4% annually.

[0003]

[0004] Methyl dihydrojasmonate, chemically named methyl 2-(pentyl-3-oxo-1-cyclopentyl)acetate, has a cyclopentanone skeleton and two chiral centers. It exists as four stereoisomers, exhibiting cis-trans isomerism. These four isomers show significant differences in aroma profile and intensity. Studies have found that the trans (1R,2R) isomer has an earthy jasmine aroma, with poorer aroma quality but a relatively strong scent; the trans (1S,2S) isomer has the weakest aroma; the cis (1S,2R) isomer also has a weak aroma; while the cis (1R,2S) isomer has a pure jasmine aroma, possessing the best and strongest aroma among the four isomers, with an intensity more than 70 times that of the trans (1R,2R) isomer and more than 1000 times that of the other two isomers. Therefore, developing efficient chemical synthesis methods to prepare cis(1R,2S)-configured dihydrojasmonic acid methyl ester has significant industrial application value.

[0005] Currently, there are two main methods for preparing high-proportion cis-dihydrojasmonic acid methyl ester: one is to directly perform an asymmetric catalytic hydrogenation reaction of dehydrojasmonic acid methyl ester to prepare high-cis-dihydrojasmonic acid methyl ester; the other is to synthesize high-cis-dihydrojasmonic acid methyl ester using cyclopentenone as a raw material. For example, Firmenich has achieved the asymmetric catalytic hydrogenation reaction of dehydrojasmonic acid methyl ester based on its developed ruthenium-catalyzed asymmetric catalytic hydrogenation reaction technology, and has industrially produced high-cis-(1R,2S)-dihydrojasmonic acid methyl ester with an ee value of 65-88% and a cis-trans isomer ratio of up to 96:4. There are also reports of directly using a Pd / C catalyst to catalytically hydrogenate dehydrojasmonic acid methyl ester to prepare dihydrojasmonic acid methyl ester, with a cis isomer ratio of 30-40%. The key intermediate in the synthesis of high-cis dihydrojasmonic acid methyl ester from cyclopentenone is 2-pentyl-2-cyclopentenone. This intermediate undergoes an asymmetric Michael addition reaction followed by subsequent transformations to obtain high-cis dihydrojasmonic acid methyl ester. However, these synthetic processes all have certain industrial production problems, such as cumbersome and costly catalyst preparation; low proportion of cis isomers, especially (1R,2S) configuration isomers, resulting in low industrial value of the product; harsh reaction conditions; long process routes; and non-compliance with green development principles. Summary of the Invention

[0006] To address the shortcomings of existing technologies, the present invention aims to provide a method for the asymmetric catalytic hydrogenation preparation of methyl cis(1R,2S)-dihydrojasmonic acid, which can synthesize high-cis-dihydrojasmonic acid methyl ester in a green and efficient manner.

[0007] This invention is achieved through the following technical solution:

[0008] A method for preparing methyl cis(1R,2S)-dihydrojasmonic acid by asymmetric catalytic hydrogenation includes the following steps:

[0009] Using methyl 3-oxo-2-pentyl-1-cyclopentene-1-acetate as a raw material, under the action of an asymmetric catalytic hydrogenation catalyst, chiral ligand, and additives, the carbon-carbon double bond is selectively hydrogenated in a solvent under a hydrogen atmosphere at a certain pressure to produce methyl cis-(1R,2S)-dihydrojasmonic acid. The crude product is then purified by distillation to obtain the final product.

[0010] The chemical reaction equation is shown below:

[0011]

[0012] A further improvement to the present invention is as follows:

[0013] The asymmetric catalytic hydrogenation catalyst is one or a mixture of two or more of the following: NiBr2, NiI2, NiF2, (MeCN)NiCl2, NiCl2·6H2O, NiSO4·6H2O, NiBF4·6H2O, NiPF6, Ni(OAc)2·4H2O, Ni(OAc)2, Ni(TFA)2, Ni(COD)2, (DME)NiBr2, (DME)NiCl2, or Ni(acac)2.

[0014] Furthermore, the chiral ligand is one or a mixture of two or more of (R)-BINAP, (R)-SegPhos, (R)-Cn-BridgePhos (n = 7-12), (R,R)-Ph-BPE, (R,R)-Me-DuPhos, (R,R)-BenzP*, (R,R)-QuinoxP*, (R,Sp)-JosiPhos, Josiphos SL-J002-1, or Josiphos SL-J009-1.

[0015] Furthermore, the additive is one or a mixture of two or more of the following: formic acid, acetic acid, propionic acid, trifluoroacetic acid, p-toluenesulfonic acid, methanesulfonic acid, tartaric acid, oxalic acid, citric acid, sodium bisulfate, and potassium bisulfate.

[0016] Furthermore, the solvent is one or a mixture of two or more of the following: methanol, ethanol, propanol, isopropanol, toluene, xylene, trimethylbenzene, tetrahydrofuran, 1,4-dioxane, ethylene glycol dimethyl ether, dichloromethane, 1,2-dichloroethane, n-hexane, cyclohexane, ethyl acetate, or methyl acetate.

[0017] Furthermore, the molar ratio of the methyl 3-oxo-2-pentyl-1-cyclopentene-1-acetate, the asymmetric catalytic hydrogenation catalyst, the chiral ligand, and the additive is 100–1000:1:1:1–2.

[0018] Furthermore, the asymmetric catalytic hydrogenation reaction is carried out at a temperature of 40–60 °C for a time of 18–24 h.

[0019] Furthermore, the hydrogen pressure is 3.0–5.0 MPa.

[0020] Furthermore, the reaction was terminated as indicated by GC.

[0021] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0022] The raw materials, catalysts, and additives used in this invention are readily available commercially. The reaction conditions are mild, and the synthetic process is simple. After the reaction, distillation yields a high proportion of methyl cis-(1R,2S)-dihydrojasmonic acid, with high product selectivity and few byproducts. It possesses advantages such as simple operation, environmental friendliness, and high product quality, making it highly valuable for industrial applications. Detailed Implementation

[0023] The present invention will now be described in detail with reference to specific embodiments.

[0024] Example 1

[0025] The following raw materials were added to a dry and clean autoclave: methyl 3-oxo-2-pentyl-1-cyclopenten-1-acetate (2.2 g, 10.0 mmol), catalyst Ni(OAc)₂·4H₂O (0.05 mmol), chiral ligand (R)-BINAP (0.05 mmol), additive acetic acid (0.05 mmol), and solvent methanol (4.0 mL). The autoclave was first pressurized with 1.0 MPa high-purity nitrogen to purge the gas three times, then purged with 1.0 MPa hydrogen three times. The pressure was then increased to 5.0 MPa with hydrogen, and the autoclave was placed in a 60°C oil bath for 24 h. After the reaction was complete, the temperature was lowered, and the gas was slowly released. The reaction solution was analyzed by GC. The conversion rate of the raw material was 93%, and the selectivity for (1R,2S)-dihydrojasmonic acid methyl ester was 90%.

[0026] Example 2

[0027] The following ingredients were added to a dry and clean autoclave: methyl 3-oxo-2-pentyl-1-cyclopenten-1-acetate (2.2 g, 10.0 mmol), catalyst NiCl2·6H2O (0.05 mmol), chiral ligand (R,R)-Ph-BPE (0.05 mmol), additive oxalic acid (0.05 mmol), and solvent trifluoroethanol (4.0 mL). The autoclave was first pressurized with 1.0 MPa high-purity nitrogen to purge the gas three times, then purged with 1.0 MPa hydrogen three times. The pressure was then increased to 3.0 MPa with hydrogen, and the autoclave was placed in a 40°C oil bath for 18 h. After the reaction, the temperature was lowered, and the gas was slowly released. The reaction solution was analyzed by GC. The conversion rate of the starting material was 95%, and the selectivity for (1R,2S)-dihydrojasmonic acid methyl ester was 92%.

[0028] Example 3

[0029] The following ingredients were added to a dry and clean autoclave: methyl 3-oxo-2-pentyl-1-cyclopenten-1-acetate (2.2 g, 10.0 mmol), catalyst Ni(OAc)₂ (0.05 mmol), chiral ligand (R)-C10-BridgePhos (0.05 mmol), additive tartaric acid (0.1 mmol), and solvent ethanol (4.0 mL). The autoclave was first pressurized with 1.0 MPa high-purity nitrogen to purge the gas three times, then purged with 1.0 MPa hydrogen three times. The pressure was then increased to 5.0 MPa with hydrogen, and the autoclave was placed in a 40°C oil bath for 20 h. After the reaction, the temperature was lowered, and the gas was slowly released. The reaction solution was analyzed by GC. The conversion rate of the starting material was 96%, and the selectivity for (1R,2S)-dihydrojasmonic acid methyl ester was 94%.

[0030] Example 4

[0031] The following ingredients were added to a dry and clean autoclave: methyl 3-oxo-2-pentyl-1-cyclopenten-1-acetate (2.2 g, 10.0 mmol), catalyst NiBF4·6H2O (0.05 mmol), chiral ligand (R,Sp)-JosiPhos (0.05 mmol), additive sodium bisulfate (0.05 mmol), and solvent tetrahydrofuran / n-hexane (2.0 / 2.0 mL). The autoclave was first pressurized with 1.0 MPa high-purity nitrogen to purge the gas three times, then purged with 1.0 MPa hydrogen three times. The pressure was then increased to 4.0 MPa with hydrogen, and the autoclave was placed in a 40°C oil bath for 20 h. After the reaction, the temperature was lowered, and the gas was slowly released. The reaction solution was analyzed by GC. The conversion rate of the starting material was 91%, and the selectivity for (1R,2S)-dihydrojasmonic acid methyl ester was 88%.

[0032] Example 5

[0033] The starting material methyl 3-oxo-2-pentyl-1-cyclopenten-1-acetate (22 g, 100.0 mmol), catalyst Ni(TFA)2 (0.1 mmol), chiral ligand (R)-SegPhos (0.1 mmol), additive trifluoroacetic acid (0.1 mmol), and solvent trifluoroethanol (25.0 mL) were added to a dry and clean autoclave. The gas was first purged three times with high-purity nitrogen at 1.0 MPa, then purged three times with hydrogen at 1.0 MPa. The pressure was then increased to 5.0 MPa with hydrogen, and the autoclave was placed in an oil bath at 50 °C for 48 h. After the reaction, the temperature was lowered, and the gas was slowly released. The reaction solution was analyzed by GC. The conversion rate of the starting material was 90%, and the selectivity for (1R,2S)-dihydrojasmonic acid methyl ester was 86%.

[0034] Example 6

[0035] The following ingredients were added to a dry and clean autoclave: methyl 3-oxo-2-pentyl-1-cyclopenten-1-acetate (2.2 g, 10.0 mmol), catalyst (MeCN) NiCl2 (0.1 mmol), chiral ligand (R)-C8-BridgePhos (0.1 mmol), additive citric acid (0.2 mmol), and solvent 1,4-dioxane (4.0 mL). The autoclave was first pressurized with 1.0 MPa high-purity nitrogen to purge the gas three times, then purged with 1.0 MPa hydrogen three times. The pressure was then increased to 3.0 MPa with hydrogen, and the autoclave was placed in a 60°C oil bath for 18 h. After the reaction, the temperature was lowered, and the gas was slowly released. The reaction solution was analyzed by GC. The conversion rate of the starting material was 96%, and the selectivity for (1R,2S)-dihydrojasmonic acid methyl ester was 92%.

[0036] Example 7

[0037] The following ingredients were added to a dry and clean autoclave: methyl 3-oxo-2-pentyl-1-cyclopenten-1-acetate (2.2 g, 10.0 mmol), catalyst Ni(COD)₂ (0.05 mmol), chiral ligand (R,R)-Me-DuPhos (0.05 mmol), additive p-toluenesulfonic acid (0.05 mmol), and solvent tetrahydrofuran (4.0 mL). The autoclave was first pressurized with 1.0 MPa high-purity nitrogen to purge the gas three times, then purged with 1.0 MPa hydrogen three times. The pressure was then increased to 4.0 MPa, and the autoclave was placed in a 40°C oil bath for 20 h. After the reaction, the temperature was lowered, and the gas was slowly released. The reaction solution was analyzed by GC. The conversion rate of the starting material was 94%, and the selectivity for (1R,2S)-dihydrojasmonic acid methyl ester was 89%.

[0038] Example 8

[0039] The following ingredients were added to a dry and clean autoclave: methyl 3-oxo-2-pentyl-1-cyclopenten-1-acetate (2.2 g, 10.0 mmol), catalyst NiBr2 (0.05 mmol), chiral ligand Josiphos SL-J002-1 (0.05 mmol), additive sodium bisulfate (0.05 mmol), and solvent n-hexane (4.0 mL). The autoclave was first pressurized with 1.0 MPa high-purity nitrogen to purge the gas three times, then purged with 1.0 MPa hydrogen three times. The pressure was then increased to 3.0 MPa with hydrogen, and the autoclave was placed in a 40°C oil bath for 20 h. After the reaction, the temperature was lowered, and the gas was slowly released. The reaction solution was analyzed by GC. The conversion rate of the starting material was 96%, and the selectivity for (1R,2S)-dihydrojasmonic acid methyl ester was 90%.

[0040] Example 9

[0041] The raw material methyl 3-oxo-2-pentyl-1-cyclopenten-1-acetate (2.2 g, 10.0 mmol), catalyst Ni(PPh3)4 (0.05 mmol), and chiral ligand (R,R)-QuinoxP were prepared. * 0.05 mmol of sodium bisulfate (0.05 mmol) and 4.0 mL of 1,2-dichloroethane (4.0 mL) were added to a dry and clean autoclave. The autoclave was first pressurized with 1.0 MPa high-purity nitrogen to purge the gas three times, then purged with 1.0 MPa hydrogen three times. The pressure was then increased to 5.0 MPa with hydrogen, and the autoclave was placed in a 60°C oil bath for 10 h. After the reaction was complete, the temperature was lowered, and the gas was slowly released. The reaction solution was analyzed by GC. The conversion rate of the starting material was 92%, and the selectivity for (1R,2S)-dihydrojasmonic acid methyl ester was 87%.

[0042] Example 10

[0043] The following ingredients were added to a dry and clean autoclave: methyl 3-oxo-2-pentyl-1-cyclopenten-1-acetate (2.2 g, 10.0 mmol), catalyst (DME) NiCl2 (0.02 mmol), chiral ligand (R)-C12-BridgePhos (0.02 mmol), additive sodium bisulfate (0.02 mmol), and solvent ethanol (4.0 mL). The autoclave was first pressurized with 1.0 MPa high-purity nitrogen to purge the gas three times, then purged with 1.0 MPa hydrogen three times. The pressure was then increased to 4.0 MPa with hydrogen, and the autoclave was placed in a 40°C oil bath for 20 h. After the reaction, the temperature was lowered, and the gas was slowly released. The reaction solution was analyzed by GC. The conversion rate of the starting material was 95%, and the selectivity for (1R,2S)-dihydrojasmonic acid methyl ester was 93%.

[0044] The above embodiments are only for illustrating the technical concept and features of the present invention, and are intended to enable those skilled in the art to understand the content of the present invention and implement it accordingly. They should not be construed as limiting the scope of protection of the present invention. All equivalent transformations or modifications made in accordance with the spirit and essence of the present invention should be covered within the scope of protection of the present invention.

Claims

1. A method for preparing methyl cis(1R,2S)-dihydrojasmonic acid by asymmetric catalytic hydrogenation, characterized in that, Includes the following steps: Using methyl 3-oxo-2-pentyl-1-cyclopentene-1-acetate as a raw material, under the action of an asymmetric catalytic hydrogenation catalyst, a chiral ligand, and additives, the carbon-carbon double bond is selectively hydrogenated in a solvent under a hydrogen atmosphere at a certain pressure to produce methyl cis-(1R,2S)-dihydrojasmonic acid. The crude product is then purified by distillation to obtain the final product. The asymmetric catalytic hydrogenation catalyst is one or a mixture of two or more of the following: NiBr2, NiI2, NiF2, (MeCN)NiCl2, NiCl2·6H2O, NiSO4·6H2O, NiBF4·6H2O, NiPF6, Ni(OAc)2·4H2O, Ni(OAc)2, Ni(TFA)2, Ni(COD)2, (DME)NiBr2, (DME)NiCl2, or Ni(acac)2. The chiral ligand is one or a mixture of two or more of the following: (R)-BINAP, (R)-SegPhos, (R)-Cn-BridgePhos (n=7-12), (R,R)-Ph-BPE, (R,R)-Me-DuPhos, (R,R)-BenzP*, (R,R)-QuinoxP*, (R,Sp)-JosiPhos, Josiphos SL-J002-1, or Josiphos SL-J009-1. The additive is one or a mixture of two or more of the following: formic acid, acetic acid, propionic acid, trifluoroacetic acid, p-toluenesulfonic acid, methanesulfonic acid, tartaric acid, oxalic acid, citric acid, sodium bisulfate, and potassium bisulfate. The hydrogen pressure is 3.0–5.0 MPa.

2. The method for preparing methyl cis-(1R,2S)-dihydrojasmonic acid by asymmetric catalytic hydrogenation according to claim 1, characterized in that: The solvent is one or a mixture of two or more of the following: methanol, ethanol, propanol, isopropanol, toluene, xylene, trimethylbenzene, tetrahydrofuran, 1,4-dioxane, ethylene glycol dimethyl ether, dichloromethane, 1,2-dichloroethane, n-hexane, cyclohexane, ethyl acetate, or methyl acetate.

3. The method for preparing methyl cis-(1R,2S)-dihydrojasmonic acid by asymmetric catalytic hydrogenation according to claim 1, characterized in that: The molar ratio of methyl 3-oxo-2-pentyl-1-cyclopentene-1-acetate, the asymmetric catalytic hydrogenation catalyst, the chiral ligand, and the additive is 100~1000:1:1:1~2.

4. The method for preparing methyl cis-(1R,2S)-dihydrojasmonic acid by asymmetric catalytic hydrogenation according to claim 1, characterized in that: The asymmetric catalytic hydrogenation reaction is carried out at a temperature of 40–60 °C for 18–24 h.

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